1. Field of the Invention
There are many steps in the biosynthesis and utilization by the tissues of testosterone. Testosterone is made mostly in the testicles. A lesser amount is made in the adrenals. Production is stimulated by secretion of Gn RH or LHRH by the brain, which causes secretion of luteinizing hormone (LH) by the pituitary, which causes the testicles to make testosterone. Testosterone then flows into the blood stream and is absorbed by the target cells. Here it binds to a receptor and is transported into the cell and converted to dihydrotestosterone. This is bound and carried to the nucleus of the cell where it redirects cellular activity by turning on and off DNA. Hormonal manipulation is a term which refers to the reduction of testosterone or its effects by blocking any step in the above process in order to gain a desired effect. Until now the uses of hormonal manipulation include for example treating prostatic carcinoma, and treatment for baldness.
2. Description of Related Prior Art
The present invention involves the use of hormonal manipulations in the prevention and treatment of atherosclerosis, coronary heart disease, stroke and peripheral vascular disease.
Leuprolide acetate is a synthetic nonapeptide of naturally occurring gonadotropin-releasing hormone (GnRH or LH—RH), the chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate salt sold under the trade name Lupron or Lupron Depot, as identified by U.S. Pat. No. 4,897,256, the entire disclosure is incorporated by reference herein, is known for use in the treatment of prostatic carcinoma. Leuprolide is a potent inhibitor of gonadotropin secretion known to decrease levels of LHRH, LH and Testosterone.
Goserelin Acetate, a synthetic decapeptide analogue of LHRH or GnRH, is chemically described as an acetate salt of [D-Ser(But)6Azygly10]LHRH. Its chemical structure is pyro-Glu-His-Trp-Ser-Tyr-D-Ser(Bu)-Leu-Arg-Pro-Azgly-NH2 acetate [C59H84N18014 (C2H4O2) sold under the trade name Zoladex, as identified by the U.S. Pat. No. 5,510,460, the entire disclosure is incorporated by reference herein, is known for the use in treatment of prostatic carcinoma. Goserelin acetate is a potent inhibitor of gonadotropin secretion known to reduce levels of GnRH or LHRH, LH and Testosterone.
Nilutamide, a nonsteroidal, orally active, antiandrogen, having the chemical name 5,5-dimethyl 3-[4-nitro-3-(trifluoromethyl)phenyl]2,3-imidazolidinedlone, sold under the trade name Nilandron, as identified by U.S. Pat. No. 5,023,088, the entire disclosure is incorporated by reference herein, is known for use in treatment of prostatic carcinoma.
Flutamide, an acetanilid, nonsteroidol androgen having the chemical name, 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide sold under the trade name Eulexin, as identified by U.S. Pat. Nos. 3,995,060 and 4,474,813, the entire disclosure of which are incorporated by reference herein, Flutamide is known for use in treatment of prostatic carcinoma.
Bicalutamide, a non-steroidal antiandrogen, chemical name is propanamide, N-(4cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-(+−) sold under the trade name Casodex, as identified by U.S. Pat. No. 4,636,505, the entire disclosure is incorporated by reference herein, is known for use in treatment of prostatic carcinoma.